SETBP1 Contributes to the Progression of Neuroblastoma Through Regulating EPHA7 Expression
摘要
Mutations in SETBP1 cause Schinzel-Giedion syndrome (SGS), which is characterized by severe mental retardation, distinctive facial features, and multiple congenital malformations. SGS neural progenitors exhibit aberrant proliferation and migration, but the underlying mechanism remains unclear. Here, we established SH-SY5Y stable cell lines of SETBP1 overexpression and knockdown. Target genes expression of SETBP1 was tested by quantitative RT-PCR and western blot. Chromatin immunoprecipitation assay and luciferase reporter assay were used to identify the binding and effect of SETBP1 to EPHA7 promoter. Cell proliferation and migration of SH-SY5Y cells were observed by cell counting kit-8 assay, colony formation assay, transwell migration assay and wound healing assay. Neuron-like differentiation of SH-SY5Y cells was detected using immunofluorescence assay. In this study, the protein expression of EPHA7 was found upregulated in SH-SY5Y cell lines with SETBP1 overexpression; in contrast, the protein expression of EPHA7 was obviously down- regulated in SH-SY5Y cell lines with SETBP1 knockdown. Moreover, the transcription of EPHA7 was mediated by SETBP1 in SH-SY5Y cells, and the -2232 bp ~ -1958 bp and -1770 bp ~ -1544 bp, was identified as two key promoter of EPHA7. SETBP1 may act through EPHA7 to enhance the neuroblastoma cell proliferation. Our results showed that the transcriptional expression of EPHA7 was regulated by SETBP1, and the SETBP1 may act through EPHA7 to promote the development of neuroblastoma, which may be one of the pathogenic mechanisms underlying neurodevelopmental disorders.